Unusual Two-Step Assembly of a Minimalistic Dipeptide-Based Functional Hypergelator

Self-assembled peptide hydrogels represent the realization of peptide nanotechnology into biomedical products. There is a continuous quest to identify the simplest building blocks and optimize their critical gelation concentration (CGC). Herein, a minimalistic, de novo dipeptide, Fmoc-Lys(Fmoc)-Asp, as an hydrogelator with the lowest CGC ever reported, almost fourfold lower as compared to that of a large hexadecapeptide previously described, is reported. The dipeptide self-assembles through an unusual and unprecedented two-step process as elucidated by solid-state NMR and molecular dynamics simulation. The hydrogel is cytocompatible and supports 2D/3D cell growth. Conductive composite gels composed of Fmoc-Lys(Fmoc)-Asp and a conductive polymer exhibit excellent DNA binding. Fmoc-Lys(Fmoc)-Asp exhibits the lowest CGC and highest mechanical properties when compared to a library of dipeptide analogues, thus validating the uniqueness of the molecular design which confers useful properties for various potential applications.     

Synthesis and Application of Methyl N,O-Hydroxylamine Muramyl Peptides

The innate immune system's interaction with bacterial cells plays a pivotal role in a variety of human diseases. Carbohydrate units derived from a component of bacterial cell wall, peptidoglycan (PG), are known to stimulate an immune response. Nonetheless, access to modified late-stage peptidoglycan intermediates is limited due to their synthetic complexity. A method to rapidly functionalize PG fragments is needed to better understand the natural host–PG interactions. Here methyl N,O-hydroxylamine linkers are incorporated onto a synthetic PG derivative, muramyl dipeptide (MDP). The modification of MDP maintained the ability to stimulate a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) immune response dependent on the expression of nucleotide-binding oligomerization domain-containing protein 2 (Nod2). Intrigued by this modification's maintenance of biological activity, several applications were explored. Methyl N,O-hydroxylamine MDP was amendable to N-hydroxylsuccinimide (NHS) chemistry for bioconjugation to fluorophores as well as a self-assembled monolayer for Nod2 surface plasmon resonance analysis. Finally, linker incorporation was applicable to larger PG fragments, both enzymatically generated from Escherichia coli or chemically synthesized. This methodology provides rapid access to PG probes in one step and allows for the installation of a variety of chemical handles to advance the molecular understanding of PG and the innate immune system.     

L-丙氨酰-L-酪氨酸二肽化学合成研究

以L-酪氨酸和L-丙氨酸为原料,苄氧羰基保护丙氨酸,甲酯保护酪氨酸,EDCI-HOBt法合成丙酪二肽,总摩尔收率（以酪氨酸计）为42%,结构经IR、APCI-MS、NMR表征。     

高甜度二肽甜味剂的合成与特性

以异香兰素为原料,经Wittig反应、常温常压催化氢化、二异丁基氢化铝还原制得中间体3-(3-羟基-4-甲氧基苯基)丙醛。S-叔丁基-L-半胱氨酸甲酯与N-叔丁氧羰基-L-天冬氨酸-4-叔丁酯经1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐以及1-羟基苯并三唑水合物缩合制得二肽化合物N-(N-叔丁氧羰基-4-叔丁酯-L-α-天冬氨酰)-S-叔丁基-L-半胱氨酸-1-甲酯,并在氯化氢-二氧六环溶液中脱保护制得二肽化合物N-(L-α-天冬氨酰)-S-叔丁基-L-半胱氨酸-1-甲酯;然后将中间体3-(3-羟基-4-甲氧基苯基)丙醛与N-(L-α-天冬氨酰)-S-叔丁基-L-半胱氨酸-1-甲酯通过亚胺化钯碳氢气常压催化氢化得到目标化合物N-[N-[3-(3-羟基-4-甲氧基苯基)丙基]-L-α-天冬氨酰基]-S-叔丁基-L-半胱氨酸-1-甲酯。经红外光谱、质谱以及核磁共振仪对产物进行结构鉴定,确定目标产物结构。     

二肽甜味剂结构的研究进展

二肽甜味剂对N-端的结构有严格的要求，C-端却是经常可以变化的。为进一步揭示二肽甜味剂的结构，分析了一系列aspartame衍生物。研究表明，苯丙氨酸上的疏水基团X当改变其结构大小时，甜度的变化不大。而肽键对于维持甜味是必需的，用酯键取代肽键导致甜味消失，氨基上的氢键对于维持甜味来说也是必需的，当它被甲基取代时甜味也消失了。     

一种新型二肽甜味剂的合成及表征

以3-环己基-L-丙氨酸、Boc-L-天冬氨酸-4-苄酯为原料合成二肽L-天冬氨酰-3-环己基-L-丙氨酸-1-甲酯(Ⅰ),以3-羟基-4-甲氧基苯甲醛为原料经过Witting反应、H2还原和DIBAL-H还原三步反应合成3-羟基-4-甲氧基苯丙醛(Ⅱ),然后Ⅰ与Ⅱ在氢气、Pd/C催化作用下进行还原氨化反应,得到目标产物N-[3-(3-羟基-4-甲氧基苯基)丙基]-α-L-天冬氨酰-3-环己基-L-丙氨酸-1-甲酯(Ⅲ),总产率为47%。产物的结构采用IR、~1HNMR、~(13)CNMR和HRMS进行表征,并验证其甜度约为蔗糖的25000倍。合成终产物的最佳工艺条件为:n(Ⅱ)∶n(Ⅰ)=1∶1,Pd/C催化剂用量为反应物总重的10%,体积分数80%的甲醇水溶液为溶剂,反应温度35℃,反应时间20 h。     

神经二肽N-乙酰天门冬氨酰谷氨酸的合成

The synthesis process of N-acetyl-aspartyl-glutamate (NAAG) was studied, in which L-aspartic acid was used as the raw material, and the dipeptide was first prepared by esterification,acylation and the reaction with L-glutamic acid, and then the product NAAG was finally obtained by hydrolyzation and purification.The product and the intermediate were analyzed and identified by melting point measuring, elemental analysis, polarimeter and IR analysis.The effects of mixture ratio of raw materials, reaction temperature and reaction time were investigated.The results showed that the total yield was 50.02% when the esterification temperature was controlled at 20℃, esterification time 10 h, acylation temperature 70℃, acylation time 2 h, and DCC was used as the addition reagent to synthesize dipeptide.The hydrolization temperature was 60℃, the hydrolization time was 4 h.The product was purified by ion-exchange resin.The purity detected by HPLC was 97.5%.     

杂三核配合物[Mg(H2O)4(CuL)2]·4H2O的合成和晶体结构

金属配体[CuL](H2L=水杨醛缩甘二肽席夫碱)和MgSO4在水-甲醇混合溶液中合成了一个Cu(Ⅱ)-Mg(Ⅱ)杂核配合物[Mg(H2O)4 (CuL)2]·4H20.用元素分析、红外光谱等手段对标题配合物的组成和结构进行了表征.该配合物属于三斜晶系,空间群是P-1,晶胞参数a=7.537(1)(A),b=9.127(2)(A),c=11.728(2)(A),a=73.55(1)°,β=72.43(1)°,γ=84.29(1)°.     

Effect of the solvent on the conformational behavior of the alanine dipeptide deduced from MD simulations

In general, peptides do not exhibit a well-defined conformational profile in solution. However, despite the experimental blurred picture associated with their structure, compelling spectroscopic evidence shows that peptides exhibit local order. The conformational profile of a peptide is the result of a balance between intramolecular interactions between different atoms of the molecule and intermolecular interactions between atoms of the molecule and the solvent. Accordingly, the conformational profile of a peptide will change upon the properties of the solvent it is soaked. To get insight into the balance between intra- and intermolecular interactions on the conformational preferences of the peptide backbone we have studied the conformational profile of the alanine dipeptide in diverse solvents using molecular dynamics as sampling technique. Solvents studied include chloroform, methanol, dimethyl sulfoxide, water and N-methylacetamide. Different treatments of the solvent have been studied in the present work including explicit solvent molecules, a generalized Born model and using the bulk dielectric constant of the solvent. The diverse calculations identify four major conformations with different populations in the diverse solvents: the C₇^eq only sampled in chloroform; the C₅ or extended conformation; the polyproline (PII) conformation and the right-handed α-helix conformation (α_R). The results of present calculations permit to analyze how the balance between intra- and intermolecular interactions explains the populations of the diverse conformations observed.     

环肽、3-苯乳酸与苯丙酸组合物对双菌生物被膜的影响

为研究植物乳杆菌CCFM8724产生的3种代谢物环亮氨酸脯氨酸二肽、3-苯乳酸、苯丙酸对变异链球菌和白色念珠菌双菌生物被膜的作用及其作用机制,测定了3种代谢物的组合物对变异链球菌和白色念珠菌双菌生物被膜量、胞外多糖和胞外蛋白产量、群体感应信号分子AI-2产量及生物被膜结构的影响,并通过分子对接的方式探究小分子代谢物结合致病菌靶点的方式和构象。结果表明:组合物的干预使变异链球菌和白色念珠菌双菌生物被膜量减少了79.4%,水不溶性胞外多糖和胞外蛋白的产量分别减少了63.8%、60.2%,群体感应信号分子AI-2产量减少了80.7%,同时破坏了生物被膜结构。分子对接结果显示:组合物可以与变异链球菌PtxA蛋白和白色念珠菌Fba蛋白的靶点结合,影响其糖代谢,进而抑制二者形成生物被膜。通过探究植物乳杆菌CCFM8724抑制双菌生物被膜潜在的物质基础,旨在从分子水平揭示组合物环亮氨酸脯氨酸二肽、3-苯乳酸、苯丙酸可能的抑菌机理,为植物乳杆菌CCFM8724及其代谢物组合物开发口腔益生菌和后生元产品提供一定的理论依据。